The mortality rate for women with ovarian cancer is very high, mainly because there is no effective method for early detection and more than two-thirds of patients have late-stage metastatic disease at the time of diagnosis. Our preliminary data suggest that plasma levels of lysophospholipids (LPL) are elevated in ovarian cancer patients, including patients with early stage disease, and thus may be useful in ovarian cancer detection. Our preliminary LPL data also show statistically significant differences in samples obtained preoperatively versus postoperatively, suggesting that some LPL may return to baseline after successful treatment and may be useful in predicting recurrence. Serum proteomic profiles (PP) have also shown early promise for ovarian cancer detection, but further investigation regarding the identity of the discriminatory proteins is needed. Thus far, published findings regarding these promising biomarkers have been based on limited numbers of convenience samples. Prior to initiation of large-scale screening studies, it is imperative to confirm these preliminary findings in carefully controlled population-based studies. We propose a population-based case-control study of 250 women with invasive epithelial ovarian cancer and 250 healthy control women matched to cases based on age, ethnicity, county of residence and menopausal status. Our aims are to: 1) Estimate the sensitivity and specificity of LPL levels (including LPA, LPI, LPC and S1P) and MALDI-based proteomic profiles for the detection of ovarian cancer, 2) Determine which LPL levels (including LPA, LPI, LPC and S1P) or proteomic profiles, alone or in combination (or in combination with CA125) best discriminate(s) between ovarian cancer and no ovarian cancer and 3) Determine whether LPL levels and/or proteomic profiles are prognostic for disease-free survival in ovarian cancer patients. Use of a well-established population-based ultra-rapid ascertainment network will greatly facilitate the project. The proposed work is expected to contribute directly to development of a blood test for detection of ovarian cancer and management of ovarian cancer patients, and thus may result in improved survival from this deadly disease.